Abstract: The present invention provides an agent, or composition containing an agent, for use in treating or preventing hypercytokinemia in a subject resulting from cytokine release from non-proliferating immune cells in blood, wherein the agent comprises: (i) an oligopeptidic compound comprising a PCNA interacting motif and a domain that facilitates the cellular uptake of said compound, wherein the PCNA interacting motif is X1X2X3X4X5 (SEQ ID NO: 1) and wherein: X1 is a basic amino acid; X2 is an aromatic amino acid; X3 is an uncharged amino acid other than an aromatic amino acid, Glycine (G) and Proline (P); X4 is any amino acid other than Proline (P), an acidic amino acid or an aromatic amino acid; and X5 is a basic amino acid or Proline (P); or (ii) a nucleic acid molecule comprising a sequence encoding the oligopeptidic compound of (i). In certain aspects the agent and compositions of the invention may be used as single agents.

Abstract: The present invention relates to a recombinant self-assembled protein comprising a target-oriented peptide and a use thereof The recombinant self-assembled protein according to the present invention, comprising a target-oriented peptide, does not require an additional process for providing target-orientedness, and is thus capable of delivering a desired drug to a target tissue or target cell without using additives, such as chemical binders or stabilizers; therefore, the protein can be used for photothermal therapy, drug delivery, imaging, or the like. In particular, according to the present invention, it is possible to prepare gold-protein nanoparticle fusions in which uniform high-density gold nanoparticles having target-orientedness are bound to protein surfaces, without an additional process of surface stabilization or process for providing target-orientedness.

Abstract: Cell penetrating peptides (CPPs) are established as a strategy to move cargoes into the interior of eukaryotic cells by engaging import machinery on the cell surface. In most cases the CPP is covalently linked to the cargo; it is common to express cargo proteins with a CPP extension. In some experiments a non-specific interactions (e.g., hydrophobic interactions) have been used to form CPP-cargo complexes, but this has numerous drawbacks. Transport is less efficient and the lack of specificity means that other macromolecules in the medium will also be internalized. This application describes the use of specific CPP labeled adaptor proteins that can be used to move a wide variety of cargoes into the cell interior. The prototype adaptor protein is calmodulin; it is small, stable and easily produced, and binds short (17 amino acid) targets with high affinity in the presence of calcium. A cargo produced with a calmodulin binding tag can be internalized efficiently by CPP tagged calmodulin.

Abstract: Coupling proteins that make strong protein-protein interactions equipped with cell penetrating peptides (CPPs) provide a convenient and powerful method to perturb cell interiors; there are many potential payloads and a broad palette of selectively membrane permeable probes. In a preferred embodiment, the coupling protein will be calmodulin or a related calcium binding protein. In a preferred embodiment, the CPP will be TAT or another CPP. In a preferred embodiment, the coupling protein will release its payload after targeting to an interior compartment. Cargo proteins can be purified by affinity methods using the same tag that allows binding by the adaptor, enabling an integrated approach with ‘gains in both function and safety. Access to cell interior compartments has potential applications in research, diagnostics, and therapeutics.

Abstract: A fusion polypeptide is disclosed, which includes: (a) a mucosa targeting polypeptide; (b) a translocating peptide for translocation; and (c) a antigenic epitope. In addition, a method for enhancing a stimulation of an immune response using the aforementioned fusion polypeptide is also disclosed.

Abstract: The present invention encompasses vaccines or compositions comprising the chimeric KSAC protein that possesses immunogenic and protective properties, and methods of use including administering to an animal the antigenic KSAC protein thereof to protect animals. The invention also encompasses methods for making and producing the soluble, disaggregated, refolded or active proteins from inclusion bodies produced from prokaryotes or eukaryotes.

Abstract: The present disclosure provides methods for releasing intracellular proteins. The method allows isolation of the protein of interest from the cell without the requirement for mechanical disruption of the cells, without the need for isolation of the cells from the culture media, and without the need for removal of the cells from the culture media.

Abstract: T cell receptors (TCRs) that have specificity for the WT1 antigen are provided. The TCRs include higher affinity TCRs that were engineered through the generation of mutational libraries of TCRs in a single-chain format, followed by selection for improved stability and affinity on the surface of yeast (i.e. directed evolution). In embodiments, the TCRs can be used in soluble form for targeted delivery in vivo, or as genes introduced into T cells in an adoptive T cell setting.

Abstract: Disclosed here includes a method for purifying a biologic composition, comprising diafiltering the biologic composition into a composition comprising phosphate buffered saline (PBS) to obtain a purified composition. The method disclosed here can be particularly useful for removing one or more impurities from the biologic composition, such as bis(2-hydroxyethyl)amino-tris(hydroxymethyl)methane (Bis-tris).

Abstract: This disclosure describes non-naturally occurring protein scaffolds and methods of making and using the protein scaffolds. In one aspect, therefore, this disclosure describes a non-naturally occurring protein scaffold that includes a plurality of structural domains and a plurality of loop regions that include an amino acid sequence that varies from a naturally-occurring loop region by at least one amino acid deletion, substitution, or addition. Generally, the structural domain or domains can include at least one ? structure and/or at least one a helix.

Abstract: A method for automated processing of a cellular product comprising target substrate cells, the method comprising providing a separation apparatus configured to associate with a disposable sterile circuit comprising a separator in communication with the cellular product.

Abstract: The present invention provides compositions and methods for regulating arterial tone based on the discovery herein of novel expression and regulation of hemoglobin alpha and cytochrome B5 reductase 3 and the effects on NO and NOS.

Abstract: The present invention relates to the microbial immunogens engineered to bear ?-gal epitope(s) for induction of potent humoral and cellular immune responses when administered to subjects having anti-Gal antibodies. In one embodiment, the present invention provides compositions and methods for propagating influenza virus in human, ape, Old World monkey or bird cells that have been engineered to express an ?1,3galactosyltransferase (? 1,3GT) gene to produce virions bearing hemagglutinin molecules containing ?-gal epitopes, to increase the immunogenicity of the influenza virus. In another embodiment, the present invention provides fusion proteins between influenza virus hemagglutinin and a microbial peptide or protein of interest, and enzymatic processing of this fusion protein to carry ?-gal epitopes, to increase the immunogenicity of the microbial peptide or protein of interest.

Abstract: The present invention provides recombinant proteins or peptides comprising a mutated listeriolysin O (LLO) protein or fragment thereof, comprising a substitution or internal deletion of the cholesterol-binding domain or a portion thereof, fusion proteins or peptides comprising same, nucleotide molecules encoding same, and vaccine vectors comprising or encoding same. The present invention also provides methods of utilizing recombinant proteins, peptides, nucleotide molecules, and vaccine vectors of the present invention to induce an immune response to a peptide of interest.

Abstract: Provided herein are methods and compositions for the treatment of melanoma using anti-tumor immune cells treated with a PTD-MYC fusion protein (e.g., an HIV TAT-MYC fusion protein).

Abstract: The present invention relates to methods and compositions for stimulating an immune response. Specifically, the present invention provides methods of inducing an immune response to bacteria of the genus Bacillus (e.g., Bacillus anthracis) in a subject (e.g., a human subject) and compositions useful in such methods (e.g., a nanoemulsion comprising Bacillus anthracis or an immunogenic portion thereof). Compositions and methods of the present invention find use in, among other things, clinical (e.g. therapeutic and preventative medicine (e.g., vaccination) and research applications.

Abstract: The disclosure relates to the field of fusion proteins. In some aspects, the invention relates to artificial fusion proteins comprising cytochrome P450 enzymes linked to reductase enzymes and uses thereof. In some aspects, the disclosure relates to compounds produced by artificial cytochrome P450 enzymes.

Abstract: Provided is a vaccine combination against multiple dengue virus serotypes and preparation thereof. The vaccine combination includes a first vaccine and a second vaccine, wherein the first vaccine includes a live-attenuated dengue virus and a live-attenuated chimeric dengue virus, and the second vaccine includes a plurality type of recombinant flagellin and envelope domain III fusion proteins, wherein an envelope domain III of each type of the recombinant flagellin and envelope domain III fusion proteins is derived from a different dengue virus serotype. Also provided is a method of preventing or treating viral infection by multiple dengue virus serotypes in a subject using the vaccine combination, including the steps of administering the first and then the second vaccines at a time interval of about 1-5 weeks.

Abstract: The invention relates to the use of a bacterial artificial chromosome (BAC) for the preparation of a vaccine, wherein the BAC comprises an inducible bacterial ori sequence for amplification of the BAC to more than 10 copies per bacterial cell. Plus a viral expression cassette comprising a cDNA of an attenuated RNA virus genome and comprising cis-regulatory elements for transcription of said viral cDNA in mammalian cells and for processing of the transcribed RNA into infectious viral RNA.

Abstract: A polypeptide and polynucleotides encoding same comprising one carboxy-terminal peptide (CTP) of chorionic gonadotrophin attached to an amino terminus of a cytokine and two carboxy-terminal peptides (CTP) of chorionic gonadotrophin attached to a carboxy terminus of a cytokine are disclosed. Pharmaceutical compositions comprising the polypeptide and polynucleotides of the invention and methods of using same are also disclosed.

Abstract: A method of treating a patient who has hepatocellular carcinoma (HCC), colorectal carcinoma (CRC), glioblastoma (GB), gastric cancer (GC), esophageal cancer, NSCLC, pancreatic cancer (PC), renal cell carcinoma (RCC), benign prostate hyperplasia (BPH), prostate cancer (PCA), ovarian cancer (OC), melanoma, breast cancer (BRCA), CLL, Merkel cell carcinoma (MCC), SCLC, Non-Hodgkin lymphoma (NHL), AML, gallbladder cancer and cholangiocarcinoma (GBC, CCC), urinary bladder cancer (UBC), and uterine cancer (UEC) includes administering to said patient a composition containing a population of activated T cells that selectively recognize cells in the patient that aberrantly express a peptide.

Abstract: The present invention provides galectin-9 variant having substantially the same bioactivity as in wild-type galectin-9 and being superior in protease stability, solubility, and yield. The galectin-9 variant according to the present invention is a protein including the following NCRD and the following CCRD composed of an N-terminal region and a C-terminal region. The C terminus of the NCRD and the N terminus of the CCRD are directly or indirectly bound to each other. The NCRD is (N1) a peptide composed of an amino acid sequence represented by SEQ ID NO: 1. The N-terminal region of the CCRD is (C-N1) a peptide composed of an amino acid sequence obtained by deletion of 1 to 17 amino acids in an amino acid sequence represented by SEQ ID NO: 3. The C-terminal region is (C-C1) a peptide composed of an amino acid sequence represented by SEQ ID NO: 5.

Abstract: The present invention relates to therapeutic compounds, such as vaccines against human papillomavirus (HPV) and in particular to DNA vaccines against HPV16 or HPV18. The invention further relates to protein construct encoding homodimeric peptides, which peptides may be released from a DNA vaccine or used separately. Further described are pharmaceutical formulations, host cells and methods for producing the vaccines, as well as methods for the treatment of various HPV induced diseases, such as cancers and infectious diseases by application.

Abstract: Disclosed are universal influenza A vaccines capable of providing broader crossprotection. The vaccine contains a fusion protein comprising tandem repeats of heterologous M2e epitope sequences that have been molecularly and genetically designed to provide broad cross-protection. The fusion protein may be incorporated into virus-like particles (VLPs) or a replicating live attenuated influenza virus vaccine, and administered alone or in combination with other influenza vaccines.

Abstract: Genetically modified non-human animals and methods and compositions for making and using them are provided, wherein the genetic modification comprises a deletion in an immunoglobulin constant region CH1 gene (optionally a deletion in a hinge region) of an IgG, IgA, IgD, and/or IgE, and wherein the mouse is capable of expressing a functional IgM. Genetically modified mice are described, including mice having a functional IgM gene and modified to have a deletion of a CH1 domain and a hinge region in a heavy chain constant domain that is not an IgM, e.g., in an IgG heavy chain constant domain. Genetically modified mice that make human variable/mouse constant chimeric heavy chain antibodies (antibodies that lack a light chain), fully mouse heavy chain antibodies, or fully human heavy chain antibodies are provided.

Abstract: Provided herein is an antibody (e.g., an isolated antibody) that specifically binds an epitope (e.g., linear epitope) within amino acids spanning the extracellular portion of human IL-13RA2. In some embodiments, the amino acids spanning the extracellular portion of human IL-13RA2 have at least 90% identity with the corresponding canine sequence of IL-13RA2. In some embodiments, the antibody specifically binds both human and canine IL-13RA2. In some embodiments, the antibody is a monoclonal antibody. In some embodiments, the antibody is a recombinant antibody. In some embodiments, the antibody is humanized. In some embodiments, the antibody is the monoclonal antibody produced by hybridoma 1E10B9 or a recombinant form thereof.

Abstract: The present invention relates in general to the field of TNF ligand family members. In more detail the present invention relates to polypeptides comprising at least three components A, each of which comprises the sequence of a TNF homology domain (THD) of a TNF ligand family member, or a functional derivative thereof, and comprising at least one component B consisting of a VL region and a VH region linked directly to each other with a linker sequence L which has a length of <12 amino acids. Furthermore, the present invention also relates to nucleic acids encoding such polypeptides and pharmaceutical compositions thereof.

Abstract: A method of manufacturing a biopolymer sensor including providing a biopolymer, processing the biopolymer to yield a biopolymer matrix solution, adding a biological material in the biopolymer matrix, providing a substrate, casting the matrix solution on the substrate, and drying the biopolymer matrix solution to form a solidified biopolymer sensor on the substrate. A biopolymer sensor is also provided that includes a solidified biopolymer film with an embedded biological material.

Abstract: The invention describes the development of more potent peptide vaccines to prevent or treat infections or cancer. Small synthetic peptides from the known sequences of viral, bacterial, parasitic or tumor antigens are modified so they can spontaneously form complexes with a synthetic nucleic acid, such as Poly IC, that functions as an immunological adjuvant. The peptide-nucleic acid complexes are dramatically more immunogenic as compared to the separate components. The procedure for developing the vaccine involves the conjugation of a synthetic peptide containing a C residue to poly-K using a bi-functional cross-linking reagent (SMCC). The peptide/poly-K complex was then formulated with CMC and poly-IC to produce a self-adjuvant vaccine that was 36-fold more effective as compared to the same peptide administered mixed with the same adjuvant (but not complexed to it).

Abstract: Disclosed herein are engineered cleavage half-domains; fusion polypeptides comprising these engineered cleavage half-domains; polynucleotides encoding the engineered cleavage half-domains and fusion proteins; and cells comprising said polynucleotides and/or fusion proteins. Also described are methods of using these polypeptides and polynucleotides, for example for targeted cleavage of a genomic sequence.

Abstract: The present invention provides new compositions and methods for preventing and treating pathogen infection. In particular, the present invention provides compounds having an anchoring domain that anchors the compound to the surface of a target cell, and a therapeutic domain that can act extracellularly to prevent infection of a target cell by a pathogen, such as a virus. The present invention also comprises therapeutic compositions having sialidase activity, including protein-based compounds having sialidase catalytic domains. Compounds of the invention can be used for treating or preventing pathogen infection, and for treating and reducing allergic and inflammatory responses. The invention also provides compositions and methods for enhancing transduction of target cells by recombinant viruses. Such compositions and methods can be used in gene therapy.

Abstract: The present invention is generally related to modified or mutated respiratory syncytial virus fusion (F) proteins and methods for making and using them, including immunogenic compositions such as vaccines for the treatment and/or prevention of RSV infection.

Abstract: The present invention provides compositions and methods for treating cancer or a metastasis thereof in a subject. In some embodiments, the methods involve administering a composition comprising therapeutically effective amount of at least one immune stimulator to the subject. In some embodiments, a combination of at least two immune stimulators is used for the treatment. In some embodiments, the combination includes an alpha thymosin peptide and an additional immune stimulator, and/or optionally one or more additional anti-cancer agents.

Abstract: The present invention is generally related to modified or mutated respiratory syncytial virus fusion (F) proteins and methods for making and using them, including immunogenic compositions such as vaccines for the treatment and/or prevention of RSV infection.

Abstract: The present invention provides compositions and methods for regulating arterial tone based on the discovery herein of novel expression and regulation of hemoglobin alpha and cytochrome B5 reductase 3 and the effects on NO and NOS.

Abstract: The genome sequences and the nucleotide sequences coding for the PWD circovirus polypeptides, such as the circovirus structural and non-structural polypeptides, vectors including the sequences, and cells and animals transformed by the vectors are provided. Methods for detecting the nucleic acids or polypeptides, and kits for diagnosing infection by a PWD circovirus, also are provided. Method for selecting compounds capable of modulating the viral infection are further provided. Pharmaceutical, including vaccine, compositions for preventing and/or treating viral infections caused by PWD circovirus and the use of vectors for preventing and/or treating diseases also are provided.

Abstract: The present invention relates to the diagnosis of autoimmune disorders, more specifically to the diagnosis of rheumatoid disorders, chronic autoimmune arthritis and even more specifically to the diagnosis of rheumatoid arthritis. A biomarker panel is provided which can be used to detect if a subject has rheumatoid arthritis. Also described are methods of identification of such biomarkers.

Abstract: The application provides new compositions and methods for stimulating the production of natural killer (NK) cells in a subject. NK cells can be selectively expanded with a combination of stimulating ligands. Methods and compositions for the administration of stimulatory ligands modified to self-insert into tumor cells, thereby stimulating an increase in the number of NK cells in proximity to a tumor, are also described.

Abstract: The present invention relates to tumor immunotherapy, in particular to tumor vaccination, using chimeric proteins comprising all or a portion of a hepatitis B virus core antigen protein and an amino acid sequence comprising an epitope derived from the extracellular portion of a tumor-associated antigen. In particular, the present invention provides virus-like particles comprising said chimeric proteins, which are useful for eliciting a humoral immune response in a subject against the tumor-associated antigen, in particular against cells carrying said tumor-associated antigen on their surface, wherein the tumor-associated antigen is a self-protein in said subject.

Abstract: Disclosed is the use of a fusion protein in drugs for stimulating differentiation of bone marrow mesenchymal stem cells to hematopoietic stem/progenitor cells, or drugs for proliferation of granulocyte hematopoietic progenitor cells. The fusion protein has a sequence as shown in SEQ ID NO: 2 or SEQ ID NO: 4. The drugs can be used for the prevention and/or treatment of (i) hematopoietic dysfunction caused by chemotherapy, (ii) hematopoietic dysfunction caused by radiotherapy, or (iii) leukopenia.

Abstract: A method of preparing a canine antibody suitable for use in the therapeutic treatment of a canine is provided. In particular, there is provided immunoglobulins which can be selected for the characteristic of whether they mediate downstream complement mediated immune activation when bound to a target antigen. Canine derived antibodies comprising specific heavy chain isotypes are provided. The invention extends to the use of the immunoglobulins of the invention in methods of treating conditions such as pain, inflammatory conditions and cancerous conditions in a canine.

Abstract: The present invention relates to specific regions of the N-terminal portion of the VAR2CSA protein and to the use of such specific regions in the prevention of pregnancy-associated malaria. The invention also provides immunogenic compositions and vaccines that are useful for preventing malaria in pregnant women.

Abstract: The present invention provides compositions comprising peptide-coupled biodegradable poly(lactide-co-glycolide) (PLG) particles In particular, PLG particles are surface-functionalized to allow for coupling of peptide molecules to the surface of the particles (e.g., for use in eliciting induction of immunological tolerance).

Abstract: BTLA-positive (“BTLA+”) lymphocyte signaling drives T cells and kills tumors. BTLA functions as a positive modulator of anti-tumor (anti-melanoma) T cell responses, The BTLA+ T cell responds against tumor or cancer cells, and, in cancer patients respond better to IL-2 than BTLA-negative cells. Hence, the BTLA-positive T cell in cancers is a positive marker for selection of enriched anti-tumor-cancer reactive T cells and can be used or applied for adoptive T-cell therapy or for therapeutic purposes.

Abstract: An aim is to produce a suitable foreign protein in egg white in transgenic birds at levels equivalent to or higher than the expression levels achieved using an ovalbumin promoter or an actin promoter, and to reduce the great burden on birds by reducing the expression at sites other than the oviduct while achieving expression sufficient to predict the expression levels before the birds reach sexual maturity. Provided is a transgenic bird containing a nucleic acid base sequence in chromosome in a cell that forms the oviduct, the sequence containing: (a) an avian endoplasmic reticulum chaperone promoter; and (b) a nucleic acid base sequence encoding a suitable foreign protein, functionally linked to the promoter. Also provided is a method for producing a suitable foreign protein, including recovering the suitable foreign protein from the transgenic bird.

Abstract: The present invention relates to RSV vaccines and methods for inducing an immune response to RSV in a subject comprising administering an RSV vaccine.

Abstract: Two-domain MHC polypeptides are useful for modulating activities of antigen-specific T-cells, including for modulating pathogenic potential and effects of antigen-specific T-cells. Exemplary MHC class II-based recombinant T-cell ligands (RTLs) of the invention include covalently linked ?1 and ?1 domains, and MHC class I-based molecules that comprise covalently linked ?1 and ?2 domains. These polypeptides may also include covalently linked antigenic determinants, toxic moieties, and/or detectable labels. The disclosed polypeptides can be used to target antigen-specific T-cells, and are useful, among other things, to detect and purify antigen-specific T-cells, to induce or activate T-cells, to modulate T-cell activity, including by regulatory switching of T-cell cytokine and adhesion molecule expression, to treat conditions mediated by antigen-specific T-cells, including treatment and/or prevention of central nervous system damage relating to stroke.

Abstract: The invention relates to antibody compositions and use of the composition to detect disease processes associated with elaboration of proteases. The reagents are directed to assessing an IgG breakdown product that is the result of such proteolytic cleavage. The invention further relates to the use of a therapeutic immunospecific for IgG protease cleavage products to restore effector function to antibody compositions that are subject to protease cleavage.

Abstract: Polypeptides comprising at least one carboxy-terminal peptide (CTP) of chorionic gonadotrophin attached to the carboxy terminus but not to the amino terminus of a coagulation factor and polynucleotides encoding the same are disclosed. Pharmaceutical compositions comprising the polypeptides and polynucleotides of the invention and methods of using and producing same are also disclosed.

Abstract: The present invention relates to an oligonucleotide which is designed on the basis of a nucleotide sequence shown in SEQ ID NO: 1 or SEQ ID NO: 2 and hybridizes with the endogenous plasmid gene of Chlamydia trachomatis, oligonucleotide primer and probe for detecting Chlamydia trachomatis, the detection method of Chlamydia trachomatis using said primer and probe, and a primer for detecting Chlamydia trachomatis of said oligonucleotide or the use to a probe design.